Pyk2 is a ˜116 kDa non-receptor tyrosine kinase polypeptide that shares a conserved domain structure with FAK (Sasaki et al., J. Biol. Chem., 270(36):21206-19 (1995) and Avraham et al., J. Biol. Chem., 270(46):27742-51 (1995)). Both FAK and Pyk2 polypeptides contain a N-terminal divergent FERM domain, a central kinase domain, a C-terminal domain with two proline-rich regions that dock numerous adapter and effector molecules (Andreev et al., Mol. Cell. Biol., 19(3):2338-50 (1999); Ren et al., J. Cell Biol., 152(5):971-84 (2001); and Kruljac-Letunic et al., J. Biol. Chem., 278(32):29560-70 (2003)) and share some, but not all, phosphorylation sites. Pyk2 polypeptides have a more limited normal tissue distribution being most highly expressed in brain, osteoclasts, and cells of hematologic lineage (Sasaki et al., J. Biol. Chem., 270(36):21206-19 (1995) and Avraham et al., J. Biol. Chem., 270(46):27742-51 (1995)). Pyk2 polypeptides have also been implicated in the invasive pathobiology of several cancers (Gutenberg et al., Acta Neuropathol. (Berl), 108(3):224-30 (2004); Zrihan-Licht et al., Int. J. Oncol., 24(1):153-9 (2004); and Hoelzinger et al., Neoplasia, 7(1):7-16 (2005)). Pyk2 polypeptides are activated by a diverse set of upstream signals most notably elevation of intracellular calcium but also by G-protein coupled receptors, growth factor receptors, and integrin mediated adhesion (Avraham et al., Cell Signal, 12(3):123-33 (2000)).